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CD138 multiple myeloma

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https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#1
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151530/successful-autologous-hematopoietic-stem-cell-transplantation-followed-by-bortezomib-maintenance-in-a-patient-with-relapsed-cd138-low-multiple-solitary-plasmacytomas-harboring-a-17p-deletion
#2
Hiroaki Kitamura, Yasushi Kubota, Kyosuke Yamaguchi, Kazuharu Kamachi, Atsujiro Nishioka, Masako Yokoo, Takero Shindo, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Solitary plasmacytoma of bone (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29113178/immunohistochemical-profile-and-prognostic-significance-in-primary-central-nervous-system-lymphoma-analysis-of-89-cases
#3
Jing Liu, Yaming Wang, Yuantao Liu, Zhe Liu, Qu Cui, Nan Ji, Shengjun Sun, Bingxu Wang, Yajie Wang, Xuefei Sun, Yuanbo Liu
The majority of primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphoma, characterized by poor prognosis. In the present study, the expression of cluster of differentiation (CD)10, B cell lymphoma (BCL)-6, multiple myeloma-1 (MUM-1), BCL-2, CD138 and Ki-67 was analyzed by immunohistochemistry in 89 Chinese PCNSL cases, and the potential prognostic significance was evaluated. CD10, BCL-6, MUM-1, BCL-2 and CD138 were positive in 16.9 (15/89), 51.7 (46/89), 92.1 (82/89), 73.3 (63/86) and 0% (0/65) of all cases, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100408/a-novel-fc-engineered-human-icam-1-cd54-antibody-with-potent-anti-myeloma-activity-developed-by-cellular-panning-of-phage-display-libraries
#4
Katja Klausz, Michael Cieker, Christian Kellner, Hans-Heinrich Oberg, Dieter Kabelitz, Thomas Valerius, Renate Burger, Martin Gramatzki, Matthias Peipp
To identify antibodies suitable for multiple myeloma (MM) immunotherapy, a cellular screening approach was developed using plasma cell lines JK-6L and INA-6 and human synthetic single-chain fragment variable (scFv) phage libraries. Isolated phage antibodies were screened for myeloma cell surface reactivity. Due to its binding characteristics, phage PIII-15 was selected to generate the scFv-Fc fusion protein TP15-Fc with an Fc domain optimized for FcγRIIIa binding. Various MM cell lines and patient-derived CD138-positive malignant plasma cells, but not granulocytes, B or T lymphocytes from healthy donors were recognized by TP15-Fc...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099494/prognostic-value-of-antigen-expression-in-multiple-myeloma-a-pethema-gem-study-on-1-265-patients-enrolled-in-four-consecutive-clinical-trials
#5
P Arana, B Paiva, M-T Cedena, N Puig, L Cordon, M-B Vidriales, N C Gutierrez, F Chiodi, L Burgos, L-L Anglada, J Martinez-Lopez, M-T Hernandez, A-I Teruel, M Gironella, M-A Echeveste, L Rosiñol, R Martinez, A Oriol, J De la Rubia, A Orfao, J Blade, J-J Lahuerta, M-V Mateos, J F S Miguel
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Amongst different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly-diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#6
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29081188/-cytogenetic-abnormalities-and-prognosis-of-532-patients-with-multiple-myeloma
#7
H Wu, H Zhang, H Y He, H Jiang, Y Y Zhao, R An, J He, R Li, J Lu, J Hou
Objective: To explore the effect of 6 common cytogenetic abnormalities on the prognosis of multiple myeloma (MM). Methods: Myeloma cells from a cohort of 532 newly-diagnosed MM patients enrolled were enriched by CD138 immunomagnetic beads, then detected 13q-, 17p-, 1q+, t (4;14), t (11;14) and t (14;16) and other common genetic abnormalities in MM by using interphase fluorescence in situ hybridization (FISH) technique to compare the influence of different genetic abnormalities on their prognoses. Results: The rate of cytogenetic abnormalities was 78...
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29079129/double-cd38-cd138-negative-multiple-myeloma
#8
Vitaliy Mykytiv, Abrar Alwaheed, Nurul Asyikin Mohd Hashim
The standard diagnosis of multiple myeloma by flow cytometry is based on selection of population of CD38(+)/CD138(+) positives cells. As the result treatment with proteasome inhibitors, CD138 may be underexpressed on atypical plasma cells. Thus, in order to improve this strategy, recently new CD138-independent method, based on CD38 positivity of plasma cells was developed. We present an unusual case of CD138(-) negative multiple myeloma which had become double CD138(-)/CD38(-) negative after treatment with daratumumab by which we would like to illustrate potential pitfalls of both strategies...
October 18, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29075086/cd138-negative-plasma-cells-in-relapsed-cns-multiple-myeloma
#9
Neha Singh, Jatin S Gandhi, Narendra Agrawal, Ajit Panaych, Narender Tejwani, Anurag Mehta
No abstract text is available yet for this article.
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29070123/-effect-of-b-lymphocyte-induced-mature-protein-1-expression-in-bone-marrow-mononuclear-cells-on-prognosis-of-patients-with-multiple-myeloma
#10
Guo-Sheng Liu, Jiao-Ping Wang, Zhi-Hua Chu, Ying-Ying Yu, Wei Zhou
OBJECTIVE: To study the effect of B lymphocyte-induced mature protein-1(Blimp1) expression in bone marrow mononuclear cells on the prognosis of patients with multiple myeloma. METHODS: Forty-eight patients with multiple myeloma from January 2014 to January 2015 were selected. The expression of Blimp1 in the bone marrow of all the patients was measured. According to the median score of Blimp1 expression level, the patients was divided into low expression group (L group, 22 cases) and high expression group (H group, 26 cases)...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29062027/harnessing-a-catalytic-lysine-residue-for-the-one-step-preparation-of-homogeneous-antibody-drug-conjugates
#11
Alex R Nanna, Xiuling Li, Even Walseng, Lee Pedzisa, Rebecca S Goydel, David Hymel, Terrence R Burke, William R Roush, Christoph Rader
Current strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on mutations or inefficient conjugation chemistries. Here we present a strategy to produce site-specific ADCs using a highly reactive natural buried lysine embedded in a dual variable domain (DVD) format. This approach is mutation free and drug conjugation proceeds rapidly at neutral pH in a single step without removing any charges. The conjugation chemistry is highly robust, enabling the use of crude DVD for ADC preparation. In addition, this strategy affords the ability to precisely monitor the efficiency of drug conjugation with a catalytic assay...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051077/cellular-proliferation-by-multiplex-immunohistochemistry-identifies-high-risk-multiple-myeloma-in-newly-diagnosed-treatment-naive-patients
#12
Scott Ely, Peter Forsberg, Ihsane Ouansafi, Adriana Rossi, Alvin Modin, Roger Pearse, Karen Pekle, Arthur Perry, Morton Coleman, David Jayabalan, Maurizio Di Liberto, Selina Chen-Kiang, Ruben Niesvizky, Tomer M Mark
INTRODUCTION: Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. PATIENTS AND METHODS: Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use...
September 20, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29049036/histone-deacetylase-inhibitor-bg45-mediated-ho-1-expression-induces-apoptosis-of-multiple-myeloma-cells-by-the-jak2-stat3-pathway
#13
Sishi Tang, Bingqing Cheng, Nana Zhe, Dan Ma, Jibing Xu, Xinyao Li, Yongling Guo, Weibing Wu, Jishi Wang
Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro...
October 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29025767/monocytes-and-granulocytes-reduce-cd38-expression-levels-on-myeloma-cells-in-patients-treated-with-daratumumab
#14
Jakub Krejcik, Kristine A Frerichs, Inger S Nijhof, Berris van Kessel, Jeroen van Velzen, Andries C Bloem, Marloes Broekmans, Sonja Zweegman, Johan van Meerloo, René J Musters, Pino Poddighe, Richard Groen, Christopher Chiu, Torben Plesner, Henk M Lokhorst, A Kate Sasser, Tuna Mutis, Niels W C J van de Donk
PURPOSE: Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma (MM) cells. The aim of this study was to investigate the clinical implications and the underlying mechanisms of daratumumab-mediated CD38 reduction. EXPERIMENTAL DESIGN: We evaluated the effect of daratumumab alone or in combination with lenalidomide-dexamethasone, on CD38 levels of MM cells and non-tumor immune cells in the GEN501 study (daratumumab monotherapy) and the GEN503 study (daratumumab combined with lenalidomide-dexamethasone)...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#15
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#16
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28924071/-a-case-of-a-solitary-plasmacytoma-extending-into-the-extradural-space
#17
Hiroshi Nakano, Koichi Kato, Shunsuke Nomura, Masanori Nakagawa, Takashi Higa, Shigeru Kadoyama, Takakazu Kawamata, Hiroshi Ujiie, Akira Teramoto
Plasmacytomas are characterized by a monoclonal proliferation of plasma cells, and constitute the bulk of multiple myeloma. A solitary plasmacytoma is a rare entity, and is even more unlikely to occur intracranially. Here we present a 62-year-old man with an intracranial tumor. Magnetic resonance imaging revealed a large mass on the surface of the right fronto-parieto-temporal region, with extradurally directed growth. The tumor was enhanced homogenously by gadolinium, with dural tail-like findings, which resembled a meningioma...
September 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28881672/mb4-2-mb4-3-transcripts-of-igh-mmset-fusion-gene-in-t-4-14-pos-multiple-myeloma-indicate-poor-prognosis
#18
Feng Li, Yong-Ping Zhai, Ting Lai, Qian Zhao, Hui Zhang, Yu-Mei Tang, Jian Hou
Multiple myeloma (MM) patients with t(4;14) is a heterogeneous group. Prognostic tools capable of predicting the outcome of patients are currently lacking. The MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. This study analyzed whether the overexpression of full-length (MB4-1) or truncated forms (MB4-2 and MB4-3) of MMSET influence the prognosis of t(4;14)(pos) MM patients. A total of 53 symptomatic t(4;14)(pos) MM patients were retrospectively analyzed...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28855983/bortezomib-resistance-in-multiple-myeloma-is-associated-with-increased-serine-synthesis
#19
Esther A Zaal, Wei Wu, Gerrit Jansen, Sonja Zweegman, Jacqueline Cloos, Celia R Berkers
BACKGROUND: The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an important role in cancer development and aid in the cellular adaptation to pharmacologically changed environments. Metabolic changes could therefore play an essential role in the development of drug resistance. However, specific metabolic pathways that can be targeted to improve bortezomib therapy remain unidentified...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28770277/quantitative-pcr-an-alternative-approach-to-detect-common-copy-number-alterations-in-multiple-myeloma
#20
M C Chillón, C Jiménez, R García-Sanz, M Alcoceba, I Prieto, M García-Alvarez, A Antón, R Maldonado, M Hernández-Ruano, M González, N C Gutiérrez, M E Sarasquete
Chromosome 1q gains and 13q deletions are common cytogenetic aberrations in multiple myeloma (MM) that confer a poor prognosis. There are several techniques for the targeted study of these alterations, but interphase fluorescence in situ hybridization (FISH) is the current gold standard. The aim of the present study was to validate quantitative PCR (qPCR) as an alternative to FISH studies in CD138+-enriched plasma cells (PCs) from MM patients at diagnosis. We analyzed 1q gains and 13q deletions by qPCR in 57 and 60 MM patients, respectively...
October 2017: Annals of Hematology
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